It’s happened time and time again — adverse events are reported from a supplement and further investigation reveals that the supplement’s actual ingredients don’t match what’s in the paperwork. Past examples include products being contaminated with pharmaceutical drugs, ingredients that are present at unexpected levels, or other ingredients that weren’t meant to be included. This can happen at different points in the supply chain, but one of the culprits is imported raw materials that are contaminated. Regardless of where in the supply chain this happens, nutraceutical companies are the ones that the U.S. Food and Drug Administration (FDA) will hold responsible for ensuing problems.
The consequences of contaminated ingredients range from mild to deadly. How do companies avoid having to deal with this? Qualifying suppliers and/or ingredients ensures that what’s received is what was ordered. This can be a complicated process, but an electronic quality management system can dramatically ease the process by providing ways to audit suppliers and track any corrective action that needs to be taken in regard to your suppliers.
To ensure that raw ingredients are pure, a nutraceuticals company must hold its suppliers to the same standard that the FDA applies to manufacturers. That is, they must perform similar checks on the quality controls, processes and corrective action plans of suppliers. Theoretically, those purchasing the ingredients should be able to rely on a certificate of analysis (CoA) from suppliers to ensure that the quality, potency and purity of the raw ingredient are sufficient. Dependence on the CoA is acceptable under current good manufacturing practices (CGMPs), but only after the supplier has been qualified to ensure that the CoA is reliable. According to 21 CFR 111.95(b)(2), companies must maintain documentation regarding supplier qualification for the purposes of relying on the CoA. However, when a business receives ingredients from suppliers all over the world, this gets complicated.
To initially qualify a supplier, the receiving company must confirm what the CoA says. Thus, any tests that the supplier runs need to be run again to ensure that the results match. The company also must confirm that the CoA includes the test method, limits of that method and the actual results. Ideally, a company should perform an on-site evaluation of its suppliers through an audit that validates the product conforms to CGMPs. However, the nutraceuticals market faces unique challenges here since so many of its raw ingredients are imported from other countries. Fortunately, the inspections by regulatory bodies of other countries can tell buyers most of what they would need to know about the supplier, if such information is available1.
Qualifying a single supplier may not seem like such a big task. But when you have dozens of suppliers, the task becomes much more difficult. Using a QMS with supplier management can help you centralize all documentation related to qualifying those suppliers. This means you can easily see a list of approved vendors, if you’ve had any corrective actions associated with those vendors, and avoid duplicating your supplier qualification efforts. The larger your organization, the more important this last point becomes. Paper-based or manual systems are at a significant disadvantage when it comes to disseminating information across multiple sites, especially complex information such as supplier qualification. A QMS automates these processes to make sure every site is aware of the latest in the qualification process.
In an ideal world, companies would qualify a supplier once and all incoming ingredients would be acceptable and conform to specifications. Unfortunately, the way things pan out is frequently far from ideal. Sometimes ingredients need to be qualified on a case-by-case basis, or there are times when a supplier deviates from the ingredient’s specifications. Fortunately, there are ways that these ingredients can still be used while maintaining compliance.
There may be times when a manufacturer uses a supplier but does not feel that the CoA is trustworthy. If this is the case and finding another supplier is infeasible, then qualifying the ingredient itself is compliant with CGMPs under the 21 CFR Part 111.75(a)(2). When dealing with an herbal ingredient, the plant part, genus and species must be verified through spectrophotometric methods. Additionally, and for non-herbal ingredients, companies must test for the chemical makeup, pesticides, heavy metals and solvent residue to make sure the ingredient conforms. This includes microbiological requirements and outlining the type of sanitization process used2.
Even qualified suppliers may have times when they deviate from specifications. These exceptions may be approved by the quality department, but performing this review once the product arrives can cause delays in your processes and put a lot of pressure on your quality department. The ingredient will have to sit in your warehouse, delaying its use in your products, pushing out the date those products are complete, and prolonging sale of those supplements. Firms can avoid this problem by using a QMS to allow suppliers to collaborate with manufacturers before the raw ingredient is even shipped. This saves time and money, especially if it turns out that this deviation cannot be approved.
Who remembers taking math tests and being docked points because not every step in the process was included in your answer? Even if your answer was right, not showing how you got to that answer led to a penalty. And among the red marks on the paper was usually the reminder to “Show your work!” The same sentiment applies to anything related to the FDA and CGMPs.
Quality is a big part of compliance, but there’s more to being compliant than producing a high-quality product. If a company carefully qualifies its suppliers or raw ingredients to ensure high quality, but can’t prove that they did, then legally it’s as though nothing was done. In an FDA inspection, the burden of proof rests on the nutraceutical company, not the FDA. Without a fully integrated QMS, manufacturers will have a hard time keeping track of the quality checks they performed, including supplier and ingredient qualification. For the least stressful inspection possible, firms should employ a QMS that centralizes all documentation which can easily be supplied to the FDA.